Using electron microscopic, histochemical and autoradiographic methods, we are examining quantitatively the interaction between regenerating capillaries and the extra-cellular matrix. Both capillaries stimulated to grow in the adult rabbit cornea and embryonic vessels developing in the chick chorioallantois are being studied. In both systems specific changes in gylcosaminoglycans (GAG) were observed to correlate with significant events in capillary development. Because of these results, and using the same methods we propose to focus our studies more intensely on the precise role played by GAG in capillary growth. The location and concentration of specific varieties of GAG will be determined in capillaries at different stages of growth, maturation and regression. The synthesis of GAG by endothelial cells and perivascular cells and the rate of deposition and turnover of these materials in the perivascular connective tissue will be measured and related to the structural development of the vessel walls. The effect that removing specific GAG from the extracellular matrix has on the structure and pattern of growth of new capillaries will be studied. The relationship between GAG synthesis, cell proliferation and structural events in the vessel wall, will be further investigated by using agents that interfere with GAG synthesis. To augment the quantitative aspects of these studies, we will develop biochemical methods for measuring GAG synthesis in growing capillaries and their associated connective tissue. To obtain additional information about the structure and development of regenerating capillaries, we will also investigate the dynamics of cell turnover and cell movement within capillary sprouts, and identify the types of inter-cellular junctions present with freeze-fracture techniques.